Merisko-Liversidge E, Sarpotdar P, Bruno J, Hajj S, Wei L, Peltier N, Rake J, Shaw J M, Pugh S, Polin L, Jones J, Corbett T, Cooper E, Liversidge G G
NanoSystems, Collegeville, Pennsylvania 19426, USA.
Pharm Res. 1996 Feb;13(2):272-8. doi: 10.1023/a:1016051316815.
Determine if wet milling technology could be used to formulate water insoluble antitumor agents as stabilized nanocrystalline drug suspensions that retain biological effectiveness following intravenous injection.
The versatility of the approach is demonstrated by evaluation of four poorly water soluble chemotherapeutic agents that exhibit diverse chemistries and mechanisms of action. The compounds selected were: piposulfan (alkylating agent), etoposide (topoisomerase II inhibitor), camptothecin (topoisomerase I inhibitor) and paclitaxel (antimitotic agent). The agents were wet milled as a 2% w/v solids suspension containing 1% w/v surfactant stabilizer using a low energy ball mill. The size, physical stability and efficacy of the nanocrystalline suspensions were evaluated.
The data show the feasibility of formulating poorly water soluble anticancer agents as physically stable aqueous nanocrystalline suspensions. The suspensions are physically stable and efficacious following intravenous injection.
Wet milling technology is a feasible approach for formulating poorly water soluble chemotherapeutic agents that may offer a number of advantages over a more classical approach.
确定湿磨技术是否可用于将水不溶性抗肿瘤药物制成稳定的纳米晶药物悬浮液，使其在静脉注射后仍保持生物有效性。
通过评估四种水溶性差、化学性质和作用机制各异的化疗药物，证明了该方法的通用性。所选化合物为：匹泊舒凡（烷化剂）、依托泊苷（拓扑异构酶II抑制剂）、喜树碱（拓扑异构酶I抑制剂）和紫杉醇（抗有丝分裂剂）。使用低能球磨机将这些药物湿磨成含1%（重量/体积）表面活性剂稳定剂的2%（重量/体积）固体悬浮液。评估了纳米晶悬浮液的粒径、物理稳定性和疗效。
数据表明将水溶性差的抗癌药物制成物理稳定的水性纳米晶悬浮液是可行的。这些悬浮液在静脉注射后物理稳定且有效。
湿磨技术是一种可行的方法，用于制备水溶性差的化疗药物，与传统方法相比可能具有许多优势。
